The proposed studies will investigate the cellular immune responses in murine hosts utilizing both an in vitro and an in vivo graft reaction system. The initial system to be studied is the C1300 neuroblastoma syngeneic host combination. Similar systems, such as female hosts bearing H-Y incompatible male skin grafts and hosts bearing theta incompatible skin grafts, will be studied subsequently. These systems were chosen because they are characterized by the failure to reject grafts despite the production of the humoral antibody. The cellular immune activity of various populations of lymphoid cells sensitized in vivo will be monitored by a modification of the microcytotoxicity assay which involves the prelabeling of target cells with 3H proline. The cellular immune responses will be compared with the humoral responses at various intervals after using such assays as immune adherence and mix agglutination. In addition populations of lymphoid cells would be sensitized in vitro and evaluated for their ability to mediate lysis of target cells in vitro as measured by 51Cm release and to destroy grafts in vivo. The lymphocytes that are sensitized in vitro would be "fractionated" into subpopulations by depletion of complement receptor lymphocytes and theta bearing cells and evaluated for their ability to mediate lysis of the appropriate target cells. BIBLIOGRAPHIC REFERENCE: Phillips, Mildred E. Tumor-specific immunogenicity of transplantable chemically induced tumors, as demonstrated by uptake of tritiated thymidine by lymphoid cells from isogenic and F1 Hybrid Mice-1,2. J. Natl. Cancer Inst., 53: 1665-1670, 1974.